NorPEN The Nordic Pharmacoepidemiological Netw ork for know ledge - - PowerPoint PPT Presentation

NorPEN

The Nordic Pharmacoepidemiological Netw ork for know ledge exchange, research and research training

Helle Kieler Centre for Pharmacoepidemiology Karolinska Institutet Sweden

Nordic countries and Nordic countries and pharmacoepidemiological pharmacoepidemiological studies studies

• Population of 24 million people

Population of 24 million people

• Homogeneous

Homogeneous – – Genetically Genetically – – Socioeconomically Socioeconomically

• National health registries

National health registries

• Public health care system (almost free of charge)

Public health care system (almost free of charge)

• Reimbursement of medicines for the whole

Reimbursement of medicines for the whole population population

• Personal Identification Numbers (

Personal Identification Numbers (PINs PINs) )

“ “The Nordic countries as a cohort The Nordic countries as a cohort” ”

ICPE August 19, 2008 in Copenhagen ICPE August 19, 2008 in Copenhagen

Pub Med Pub Med

• Search terms

Search terms

– – “ “Nordic countries epidemiology Nordic countries epidemiology” ” 34 783 34 783 – – “ “Nordic countries Nordic countries pharmacoepidemiology pharmacoepidemiology” ” 110 110

• 8 abstracts

8 abstracts – – comparisons of drug use comparisons of drug use

Nordic registers on dispensed medicines Nordic registers on dispensed medicines

65 years

2008 Nordic School of Public Health Gothenburg, Sweden

Strong environment for Strong environment for population based and population based and cross cross-

• country comparative research in

country comparative research in pharmacoepidemiology pharmacoepidemiology

Organisation Organisation

Steering group Steering group

Max Petzold, SE Max Petzold, SE Mette N Mette Nø ørgaard, DK rgaard, DK Morten Morten Andersen,DK Andersen,DK Timo Klaukka, FI Timo Klaukka, FI Sirpa Hartikainen, FI Sirpa Hartikainen, FI Magn Magnú ús s J Jó óhansson hansson, IS , IS Kari Furu, NO Kari Furu, NO Gunilla Ringb Gunilla Ringbä äck Weitoft, SE ck Weitoft, SE Helle Kieler, SE Helle Kieler, SE

Reference group Reference group

Prominent senior researchers in epidemiology & pharmacoepidemiology

Forum Forum

Supervisors and PhD students Supervisors and PhD students

Collaborators Collaborators

Database holders Authorities ENCePP

NorPEN NorPEN

• Document, facilitate and promote Nordic

Document, facilitate and promote Nordic pharmacoepidemiological pharmacoepidemiological research initiatives research initiatives

• Increase quality of research and

Increase quality of research and methodological development methodological development

• Create an interactive forum for PhD

Create an interactive forum for PhD-

• students

students and supervisors and supervisors

• Assist researchers

Assist researchers

– – Initiating and designing new studies Initiating and designing new studies – – Improving quality Improving quality – – Avoiding common pitfalls and duplication of Avoiding common pitfalls and duplication of efforts efforts

NorPEN NorPEN

• Research documentation

Research documentation

– – Annual reviews of published studies, research groups, Annual reviews of published studies, research groups, centers working with the Nordic registers on dispensed centers working with the Nordic registers on dispensed medicines medicines

• Voluntary pre

Voluntary pre-

• registration of register based studies

registration of register based studies within the Nordic countries within the Nordic countries

• Overview of

Overview of organisation

• rganisation and content of the Nordic

and content of the Nordic national registers national registers

– – Process to obtain permission to access the register data Process to obtain permission to access the register data – – Identify obstacles to register based research Identify obstacles to register based research

• Web

Web-

• based system for publishing of basic

based system for publishing of basic information information -

• www.nordically.org

www.nordically.org. .

Prioritised Prioritised research areas research areas

• Rare exposures and rare events

Rare exposures and rare events

• Prescribing quality indicators

Prescribing quality indicators

• Reproductive health

Reproductive health

• Medicine use in children

Medicine use in children

• Mental health

Mental health

Meetings and workshops Meetings and workshops

• 1. March 2009, Gothenburg, Sweden
• 1. March 2009, Gothenburg, Sweden

Kick Kick-

• off meeting
• ff meeting

Research with prescription medicine registers Research with prescription medicine registers Open invitation to Nordic researchers within the area Open invitation to Nordic researchers within the area

• 2. October 2009, Helsinki/Tampere, Finland
• 2. October 2009, Helsinki/Tampere, Finland

Reproductive health, medicine use in pregnancy Reproductive health, medicine use in pregnancy

• 3. March 2010, Oslo, Norway
• 3. March 2010, Oslo, Norway

Prescribing quality indicators Prescribing quality indicators Advanced methods for analysis of medicine use pattern in databas Advanced methods for analysis of medicine use pattern in databases es

• 4. October 2010, Reykjav
• 4. October 2010, Reykjaví

ík, Iceland k, Iceland Medicine use in children Medicine use in children

• 5. March 2011, Odense, Denmark
• 5. March 2011, Odense, Denmark

Rare exposures and rare events Rare exposures and rare events

• 6. October 2011, Gothenburg, Sweden
• 6. October 2011, Gothenburg, Sweden

Mental health and psychotropic medicine use Mental health and psychotropic medicine use

Nordic study on Nordic study on SSRIs SSRIs and risks and risks

• f Congenital Malformations,
• f Congenital Malformations,

Abortions, Abortions, Perinatal Perinatal Death and Death and PPHN PPHN

Background Background

Congenital Congenital Malformations Malformations

Most studies found no statistical significant Most studies found no statistical significant increased risks for congenital malformations in increased risks for congenital malformations in users of users of SSRIs SSRIs Major limitations in previous studies Major limitations in previous studies

– – Low statistical power Low statistical power – – Uncertain information on exposure Uncertain information on exposure – – Exploratory analyses Exploratory analyses

Reported positive findings Reported positive findings

Any SSRI

Malformations1 Cystic kidneys2 Anencephaly3 Craniosystosis3 Omphalocele3 ASD9

1Wogelius, 2006, 2Källén, 2007, 3Alwan, 2007, 4Chambers, 1996, 5GSK, 2005, 6Bérard, 2007, 7Louik, 2007, 8Diav-Citrin, 2008, 9Oberlander, 2008

Fluoxetine

>2 minor anomalies4 Cardiovascular malformations8

Paroxetine

Malformations5,6 Cardiac malformations2,3,5,6,7 Neural-tube defects7 Clubfoot7

Sertraline

Omphalocele7 Septal defects7 Anal atresia7 Limb-reduction7

Citalopram

>2 minor anomalies4 Cardiovascular malformations9

Background Background

Persistent Pulmonary Hypertension of the Newborn Persistent Pulmonary Hypertension of the Newborn

ICD -10 P29.3B Term and post-term infants Incidence 1-2/1000 Mortality rate 15%

Reported findings Reported findings

Persistent Pulmonary Hypertension of the Newborn Persistent Pulmonary Hypertension of the Newborn

• 3 studies

3 studies

– – Cohort study (Chambers, 1996) Cohort study (Chambers, 1996)

• 2.7% PPHN among

2.7% PPHN among Fluoxetine Fluoxetine exposed exposed compared with expected rate of 0.1% compared with expected rate of 0.1%

– – Case control study (Chambers, 2006) Case control study (Chambers, 2006)

• OR = 6.1 (95% CI 2.2

OR = 6.1 (95% CI 2.2 – – 16.8) 16.8)

– – Cohort study ( Cohort study (K Kä ällen llen, 2008) , 2008)

• “

“RR RR” ” = 2.7 (95% CI 0.9 = 2.7 (95% CI 0.9 – – 6.3) 6.3)

Nordic study on Nordic study on SSRIs SSRIs

• Design

Design Cohort Cohort study study -

• 2

2 sub sub-

• studies

studies

• Data

Data Nordic Health Registries Nordic Health Registries

• Infants born in DK, FI, IS, NO or SE 1994

Infants born in DK, FI, IS, NO or SE 1994-

• 2007

2007

• Abortions > Gestational week 13 (FI, NO, DK)

Abortions > Gestational week 13 (FI, NO, DK)

• Outcomes

Outcomes 1. 1. Malformations Malformations, perinatal , perinatal deaths deaths, , abortions abortions 2. 2. PPHN PPHN

Prescribed Drug Register Medical Birth Register FI DK NO 1994 2007 1995 2004 SE 2005 Malformation Register Abortion Register Patient Register Psychiatry Register Neonatal Register Cause of Death Register IS 2003

FI - 1994 PDR ( > 10 €) MBR (┼: gw 22, 500g+) Malformation Register Abortion Register (induced, + indication) PtR CDR SE - 2005 PDR MBR (┼: gw 28, ÷ alcohol) PtR (“psychiatric diagnoses”) CDR DK - 1995 PDR MBR (┼: gw 22, induced abortions, ÷ BMI) PtR Psychiatry Register CDR NO - 2004 PDR MBR (┼: gw 12, sp + induc abortions + indic, “smoking”) Neonatal Register CDR IS – 2003 PDR (÷ dosage) MBR PtR CDR

Congenital malformations, Congenital malformations, abortions abortions

Pregnant women in DK, FI, IS, NO, SE

Dispensed SSRI YES NO LMP 90 d 90 d 180 d Psychiatric diagnosis YES NO Birth

PPHN PPHN

All births in DK, FI, IS, NO, SE

Dispensed SSRI YES NO LMP 140d Psychiatric diagnosis YES NO Birth 90d

3INF

Infliximab and Infections in Infants

Specific aims

Birth outcomes in newborns exposed to TNF-blockers – Gestational length – SGA – Apgar scores – Mode of delivery – Malformations

• Risk of infections in infants exposed to TNF-blockers

– All infections – Specific infections – Antibiotic use

ICPE August 19, 2008 in Copenhagen ICPE August 19, 2008 in Copenhagen

Number (%) Number (%) Number (%) Cesarean section 12 (48) 1643 (24) 66207 (16) Preterm delivery* 6 (24) 546 (8) 3236 (5) SGA delivery** 2 (11) 215 (3) 1436 (2) Infant infections*** 3 (12) 483 (9) 3899 (7) Malformations 1 (4) 267 (4) 2295 (3)

* < 37 weeks ** < 2 SD from mean birth weight *** Hospital admissions until 1 year of age

Exposed to Anti-TNF Disease controls Healthy controls N = 25 N = 6938 N = 66207

Conclusion Only 25 infants born in Denmark or Sweden 1998-2006, had been exposed prenatally to anti-TNF agents. Data is too sparse to draw any conclusions concerning safety of anti-TNF during pregnancy to date Results

NorPEN